Technical Abstract:
Background. Influenza H7 subtype is known to be enzootic among wild birds of North America and Europe as well as in live poultry markets in the USA. Sporadically, the H7 viruses are transmitted to humans. In 2002, a low pathogenic avian influenza H7N2 outbreak affected commercial poultry in Virginia. Serologic evidence of infection with the same avian H7N2 virus was found in one poultry worker during the outbreak. In 2003, H7N2 virus was isolated from a patient in New York hospitalized with respiratory tract illness. H7 virus infections in humans could start a pandemic if the virus acquires person-to-person transmissibility. For this reason, development of a human H7N2 vaccine is urgent. The purpose of this project is to develop a H7N2 influenza virus vaccine that can safely be used in humans for protection in case of pandemic.
Methods. Using the classic reassortment approach, a vaccine seed (A/H7N2-PR8) was created containing the internal genes from human vaccine strain A/Puerto Rico/8/34 (H1N1) and external genes from low pathogenic A/Turkey/Virginia/4529/02 (H7N2) influenza viruses. The vaccine was tested to assess its antigenicity in ferrets and safety in mice and chickens. Mice immunized with formalin inactivated A/H7N2-PR8 virus were challenged with viruses of distinct lineages A/Canada/444/04 (H7N3) and A/Netherlands/219/03 (H7N7) to determine the protective efficacy of the vaccine candidate.
Results. A high growth reassortant A/H7N2-PR8 was generated by conventional reassortment in embryonated eggs. The A/H7N2-PR8 virus displayed low pathogenicity in mice and chickens. Hemagglutination inhibition tests using ferret antibodies raised against A/H7N2-PR8 showed broad cross-reactivity with divergent H7 viruses of different years and lineages. Mice immunized with A/H7N2-PR8+alum were protected when challenged with either North American A/Canada/444/04 or Eurasian A/Netherlands/219/03 viruses.
Conclusions. The results indicate that inactivated A/H7N2-PR8 can be safely used as a vaccine in case of a pandemic. Immunization of mice showed protection against a heterologous challenge with a highly divergent strain of the Eurasian lineage.